Restless leg syndrome treatment

ABSTRACT

The present invention describes a method of treating restless leg syndrome by eliminating venous reflux in an underlying vein. The malfunctioning vein can be removed or ablated by inserting a catheter into the vein that transmits sufficient energy to coagulate or ablate the lining of the vein causing it to permanently close, eliminating the source of venous reflux and the symptom of restless leg syndrome.

RELATED APPLICATIONS

This Application is related to pending U.S. Provisional PatentApplication Ser. No. 60/825,687 filed Sep. 14, 2006 entitled RESTLESSLEG SYNDROME TREATMENT. This application is also a continuation-in-partof and claims benefits of U.S. patent application Ser. No. 10/982,504,filed on Nov. 4, 2004, and titled “ENDOVENOUS CLOSURE OF VARICOSE VEINSWITH MID INFRARED LASER”, which application is a continuation-in-part ofand claims the benefit of International Application NumberPCT/US2003/035178, filed under the Patent Cooperation Treaty on Oct. 30,2003, titled “ENDOVENOUS CLOSURE OF VARICOSE VEINS WITH MID INFRAREDLASER”, which application claims the benefit of U.S. Provisional PatentApplication Ser. No. 60/422,566 filed Oct. 31, 2002, entitled“ENDOVENOUS CLOSURE OF VARICOSE VEINS WITH MID INFRARED LASER”, each ofwhich applications is incorporated herein by reference in its entiretyand claims any and all benefits to which it is entitled therefrom. ThisApplication is also a continuation-in-part of U.S. application Ser. No.10/699,212 filed Oct. 30, 2003, entitled “ENDOVENOUS CLOSURE OF VARICOSEVEINS WITH MID INFRARED LASER”, which application claims the benefit ofU.S. Provisional Patent Application Ser. No. 60/422,566 filed Oct. 31,2002, entitled “ENDO VENOUS CLOSURE OF VARICOSE VEINS WITH MID INFRAREDLASER”, each of which applications is incorporated herein by referencein its entirety.

FIELD OF THE INVENTION

This invention relates to methods and apparatus for treating restlessleg syndrome (RLS). Specifically the method includes eliminating venousreflux in a vein in the leg by closing it with energy derived from aradio frequency generator, using a foam sclerosant, and using anelectrical resistance circuit or a laser.

BACKGROUND OF THE INVENTION

RLS is a poorly understood disorder in which patients experiencecompelling urges to move the legs usually accompanied by intense,unpleasant sensations in their legs. RLS affects 5-15% of the Americanand European populations. RLS affects the general population with a meanage at onset of 27.2 years. Onset of RLS is often before age 20 in 38.3%of patients. Women are twice as likely to be affected. The earliestdescription of an RLS case was by English physician and anatomist SirThomas Willis in 1672. RLS lingered in anonymity until 1944, whenSwedish neurologist Karl Ekbom first described the salient features. In1945 he coined the phrase “restless legs”. The addition of the word“syndrome” designates this malady as a condition defined by clinicalsymptoms rather than by any specific pathological process.

Most patients find they cannot describe the nature of their sensations.It is frequently unrecognized or misdiagnosed and therefore widelyundertreated. Dr. Ekbom felt that “this is evidently due to the factthat the sensations do not resemble any known phenomenon that can beused as a comparison.” They are variably described as heebie-jeebies,antsy, Jimmy legs, or as creeping-crawling, pulling, drawing, boring,wormy, etc. The sensations are painful in about 30% of patients.Patients experience intense unpleasant sensations deep in the legs thatare accompanied by an irresistible urge to move the affected limbs. Thesensations are usually located in the calf area, but may be feltanywhere from the ankles to the thighs. The arms are rarely involved.

There is a wide variation in severity with some patients experiencingonly occasional mild symptoms, while others struggle with disablingepisodes on a nightly basis. Symptoms of RLS are worse in the eveningand during periods of relaxation or decreased activity, especially whilelying down or reclining. Patients are often completely asymptomatic inthe morning. The reason for this is unknown. The desire to relieve thesymptoms can lead to a compulsion involving excessive limb movements.The sensations and the compulsion to relieve them frequently becometerribly distressing. As RLS symptoms are stronger at bedtime,sleep-onset insomnia is common. RLS sufferers often find they cannotsleep until the early morning hours. Patients with severe RLS experiencenightly attacks that lead to chronic sleep-deprivation with itsaccompanying psychological and cognitive deficits.

Investigators have made great strides in the understanding and treatmentof RLS over the last two decades, to the nightly relief of millions ofvictims. The etiology of RLS remains elusive, however, and a finalcommon pathway has yet to be described. According to Dr M. J. Thorpy,primary RLS “may represent a heterogeneous group of disorders because nosingle pathophysiologic mechanism explains all the clinical featuresexhibited.”

There are no classic physical findings, no conclusive blood assays, andno standard radiological or sleep studies to diagnose RLS. Because thereis no known biomarker, the diagnosis of RLS can only be made based onclinical history. In an attempt to more clearly define RLS, the IRLSSGdeveloped RLS diagnostic criteria in 1995. An IRLSSG consensus panel atthe National Institutes of Health (NIH) modified these criteria to theirpresent form in 2003. These four criteria are necessary and sufficientfor the diagnosis of RLS. They include: 1) Urges to move the limbs withor without unpleasant sensations, 2) worsening of symptoms at rest, 3)improvement of symptoms with movement, and 4) worsening of symptoms atnight. The IRLS questionnaire (FIG. 1) was developed by the IRLSSG andvalidated in 2003 as a consistent, reliable tool to objectively measureRLS severity.

RLS is divided into primary (idiopathic) and secondary causes. PrimaryRLS is felt to be the most common form and is suspected to be asensorimotor abnormality associated with central nervous systemdysfunction involving abnormal brain iron metabolism and irregularity ofcentral dopaminergic neurotransmitter pathways. Primary RLS likelyrepresents a heterogenous group because no single pathophysiologicmechanism explains all the clinical features exhibited. Secondary RLSoccurs in such disparate conditions as back pain, iron deficiency, renalfailure, pregnancy, neuropathy, and venous disease. Various medicationsare known to precipitate RLS attacks. The fact that RLS is a “mixed bag”diagnosis has complicated research, confounded investigators, andfrustrated clinicians; in that various medications work in only apercentage of affected patients. Current treatment therefore focuses onnightly management of symptoms rather than on cure.

In 1995, Dr. A. H. Kanter's groundbreaking study suggested thatsclerotherapy in patients with varicose veins and RLS is 98% effectivein initial relief of RLS. This is the first article to describeoperative treatment of RLS. Dr Kanter concluded that all RLS patientswith varicose veins should be considered for phlebological evaluationand possible treatment before being consigned to chronic drug therapy.

Secondary RLS is known to occur in and is secondary to such disparateconditions as iron deficiency, renal failure, pregnancy, neuropathy, andvenous insufficiency. Various medications are known to exacerbateexisting RLS, even precipitate RLS, and other causes are likely.

Because RLS is a “mixed bag” diagnosis, research investigators have beenconfounded when treatments only work on a portion of the test subjects.Treatment of the secondary causes of RLS can frequently cure patients ofthis distressing malady. Because venous insufficiency is a secondarycause, treatment of this cause may cure the patient of RLS.

Venous insufficiency is quite common, affecting 10-15% of adult men and20-25% of adult women. Duplex ultrasound studies reveal that saphenousvein reflux is the most common form of venous insufficiency and is theunderlying condition in most patients suffering with varicose veins.Sclerotherapy in patients with varicose veins and RLS has been shown tobe 98% effective in initial relief of RLS with recurrence rate of 8% and28% at one and two years, respectively. Sclerotherapy is not a veryeffective treatment for varicose veins. While effective for tiny surfaceveins, the injection of liquid sclerosant into the large veinsresponsible for venous insufficiency has a low success rate. This methodrequires multiple injections, can be very painful, and the veins oftenreopen in a few years requiring, continual treatments. Most RLS patientsare not willing to undergo this therapy. Although prior art consists ofdrug therapy and occasionally the use of compression stockings, surgeryin the form of vein stripping has also not been considered a treatmentfor this condition because of the significant morbidity associated withthe procedure. This invention discloses the use of a new minimallyinvasive treatment for venous insufficiency that is benign enough to beconsidered as a treatment and a cure for RLS with a significantlyimproved benefit to cost ratio.

Varicose veins have been treated in a similar manner except that theclinical symptoms of varicose veins are much more evident. Bulgingveins, ulcers, pain and leg tiredness are all symptoms of varicose veindisease. This invention also relates to otherwise healthy legs that donot necessarily show these symptoms but rather an early stage of venousdisease that causes RLS without bulging and painful varicose veins.

This connection between venous insufficiency and restless leg syndromehas been noted in the literature but the root cause of the disease andthe connections to the venous system is not obvious. It was only throughanecdotal comments by patients who had restless leg syndrome and werealso successfully treated for varicose veins that the connection becameclear. The restless leg symptoms disappeared after treatment forvaricose Veins. This invention takes this one step farther and claimsthat restless legs can be successfully treated even without the symptomsof varicose veins by eliminating venous reflux in a segment adjacent tothe twitching or skin movement.

ADVANTAGES AND SUMMARY OF THE INVENTION

This invention describes a method to cure Restless Legs Syndrome (RLS)in a percentage of patients without the expense and pain associated withsurgery and with far better short and long term results than the use ofliquid sclerotherapy. This new method promises to become the treatmentof choice to enable RLS patients to be taken off of debilitating andexpensive drug therapy that only treats the symptoms of RLS.

It is an advantage of the present invention to provide a method oftreating restless leg syndrome in which the method comprises the step ofeliminating reflux from an underlying vein. It is a further advantage ofthe present invention to provide said method in which the step ofeliminating reflux from an underlying vein comprises closing anunderlying leg vein with energy to eliminate venous reflux. In anembodiment of the present invention, the energy is of the type selectedfrom the group consisting of infrared, ultraviolet, visible, radiofrequency, ultrasound and laser. In an embodiment of the presentinvention, the step of eliminating reflux from an underlying veincomprises using an endovenous catheter to deliver energy to a segment ofincompetent vein. In an embodiment of the present invention, step ofeliminating reflux from an underlying vein comprises uses foamsclerotherapy.

It is an advantage of the present invention to provide a method oftreating restless leg syndrome wherein the step of using laser energy toeliminate reflux in a short segment of vein around the symptomaticregion.

It is yet another advantage of the present invention to provide a methodof treating restless leg syndrome comprising the step of eliminatingvenous reflux in an underlying vein in the absence of vein varicosities,ulcers or other visible symptoms.

It is yet another advantage of the present invention to provide anendovenous method of treating restless leg syndrome comprising the stepof using a laser having a wavelength between about 1.2 and about 2.7 umto heat and shrink collagen in a vessel wall, and in which the step ofdelivering the laser energy with a fiber optic laser delivery device. Anembodiment of the invention comprises the steps of inserting a fiberoptic laser delivery device into the vein and using a pullback device toretract the fiber optic laser delivery device through the vein at a rateof between about 0.1 mm/sec and about 10.0 mm/sec while simultaneouslydelivering laser energy therefrom. In an embodiment of the invention,the fiber optic laser delivery device is retracted at a rate of betweenabout 0.5 mm/sec and about 5.0 mm/sec. In another embodiment of theinvention, the pullback device is left off initially to let heat buildup at the start therefore enabling a better closure of the vessel. It isan advantage to remove blood from the vein prior to treatment with laserenergy. It is yet a further advantage to introduce the fiber optic laserdelivery device to the vein through an introducer catheter. In anembodiment of the present invention, a pulsed laser is used, the pulsewidth between 1 and 5000 microseconds.

Further details, objects and advantages of the present invention will become apparent through the following descriptions, and will be includedand incorporated herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a representative schematic block diagram of an embodiment ofan apparatus 100 of the present invention for performing of a varicosevein closure procedure of the present invention.

FIG. 2A is a representative view of varicosed veins 200 to be treatedaccording to the method and apparatus of the present invention.

FIG. 2B is a representative view of the GSV 202 to be treated accordingto the method and apparatus of the present invention.

FIG. 3A is a representative view showing the beginning of the introduceror dilator 300 for percutaneous access according to the method andapparatus of the present invention.

FIG. 3B is a representative view showing the use of the introducer ordilator 300 with the laser fiber 306 passing through the lumen 302 ofthe dilator 300 and into the GSV 202 according to the method andapparatus of the present invention.

FIG. 4 is a representative view of the use of an ultrasound device 400according to the method and apparatus of the present invention.

FIG. 5 is a representative view of the non-contact thermal sensor 600and the cooling system 602 of the method and apparatus of the presentinvention.

FIG. 6 shows curves for absorption coefficients of melanin, hemoglobinand water as a function of wavelength according to the method andapparatus of the present invention.

DETAILED DESCRIPTION OF

-   1. Perform and document a thorough exam of all veins contributing to    vascular insufficiency and reflux.-   2. Obtain percutaneous access of the vessel being treated using a    Seldinger Technique. The length and size access devices will vary    depending on the length and size of vein being treated and the fiber    selected.-   3. Advance catheter    -   Advance the catheter through the introducer sheath until it is        approximately 1-2 cm below the saphenofemoral junction (SFJ) or        the saphenopopliteal junction (SPJ) or at the appropriate        distance based on the junction or vein being treated.    -   Confirm position of the catheter tip with ultrasound.    -   Visualize the aiming beam through the patient's skin (the room        lights may need to be darkened at this point for adequate        visualization).-   4. Once the catheter is in the desired position, the following    methods should be used to reduce vein size:    -   Position patient in 20°-30° Trendelenburg or equivalent. It will        be understood that this typically refers to a supine position        with the patient inclined at an angle of 0-45 degrees, so that        the pelvis is higher than the head, used during and after        operations in the pelvis or for shock.    -   Elevate the extremity being treated    -   Use a syringe to suction vein contents through the access device        port    -   Use a compression wrap    -   Manual compression-   5. Inject local anesthesia around the vein being treated    -   Using ultrasound, observe infiltration of tumescent anesthesia        solution around the vein.    -   The vein should be completely surrounded with at least 10 mm of        fluid to provide thermal protection for the surrounding tissue.-   6. Remove or pull out any introducer sheath, leaving just the    proximal tip just at the skin edge of the access site    -   Removal of the sheath will prevent the catheter from entering        the sheath during the automatic pull-back.    -   Reconfirm tip position once the sheath has been pulled out.-   7. Begin treatment and observe tissue response under ultrasound    observation. If the desired tissue effect in the vein is not seen,    increase wattage. Indications of adequate tissue response include:    -   Slowing or stopping of forward movement of flow    -   Thickening of the vein wall    -   Contraction of the vein    -   Decrease in size of the vein lumen-   8. Continue to observe the aiming beam through the skin and the    tissue effect in the vein with the ultrasound. Place fingers on    either side of the catheter at the exit point from the skin to    verify movement and to support the fiber as it is being pulled out.-   9. Following the treatment, observe the appearance of the vein with    the ultrasound:    -   Vein appears more dense and thickened (more echogenic)    -   Vein is less compressible with pressure from the ultrasound        probe    -   Vein lumen is noticeably smaller in size    -   Vein does not demonstrate spontaneous flow-   10. Apply dressings at the completion of the procedure:    -   Steri-Strips®    -   Absorbent dressing over access site    -   3-inch self-adherent tape wrap    -   30-40 mm Hg compression hosiery should be placed over dressings        with the patient lying down.        Devices and Equipment:

As described above, the tissue may be heated or treated with anyoperative heating device. These include, but are not limited to thefollowings: a laser diode or other laser source, electrical current,radiofrequency waves, microwaves, ultrasound or other source ofelectromagnetic energy which penetrates into regions of tissue, byconduction or convection as with bubble generation in blood, contactdevice, active or passive heating means, etc., thus preferentiallyheating a region of tissue without excessive or otherwise undesirableheating of or effect on surrounding tissue.

Examination of veins and diagnosis of RLS is taught by Allen R P, AbetzL, Washburn T, Early C J. THE IMPACT OF RESTLESS LEGS SYNDROME (RLS) ONSLEEP AND COGNITIVE FUNCTION. Eur J Neurol. 2002; 9(suppl2):50, which ishereby incorporated herein by reference in its entirety, withoutlimitations.

Use of ultrasound for intravenous catheter or other structurevisualization, catheter positioning and treatment device, structure andfunction is further taught by U.S. Pat. No. 6,024,703 filed May 7, 1997entitled ULTRASOUND DEVICE FOR AXIAL RANGING, which is herebyincorporated herein by reference in its entirety, without limitations.

Percutaneous access of vessels methods, device, structure and functionis further taught by pending U.S. patent application Ser. No. 10/699,212filed Oct. 30, 2003 entitled ENDOVENOUS CLOSURE OF VARICOSE VEINS WITHMID INFRARED LASER, which is hereby incorporated herein by reference inits entirety, without limitations.

Automatic, motorized or other equivalent pull-back method, device,structure and function is further taught by pending U.S. patentapplication Ser. No. 10/699,212 filed Oct. 30, 2003 entitled ENDOVENOUSCLOSURE OF VARICOSE VEINS WITH MID INFRARED LASER, which is herebyincorporated herein by reference in its entirety, without limitations.

FIG. 1 is a representative schematic block diagram of the apparatus 100of the present invention for performing the varicose vein closureprocedure of the present invention. As shown, the system 100 of thepresent invention includes a laser console 102, a motorized, fiber opticcatheter “pull-back” machine 104, a fiber optic catheter or other laserdelivery device 106 to deliver laser energy into the patient's vein, asterile field 108 and a controller 110.

FIG. 2A is a representative view of varicosed veins 200 to be treatedaccording to the method and apparatus of the present invention. FIG. 2Bis a representative view of the GSV 202 to be treated according to themethod and apparatus of the present invention. FIG. 3A is arepresentative view showing the beginning of the introducer or dilator300 for percutaneous access according to the method and apparatus of thepresent invention. FIG. 3B is a representative view showing the use ofthe introducer or dilator 300 with the laser fiber 306 passing throughthe lumen 302 of the dilator 300 and into the GSV 202 according to themethod and apparatus of the present invention.

FIG. 4 is a representative view of the use of an ultrasound device 400according to A method and apparatus of the present invention. FIG. 5 isa representative view of a physician 500 performing manual compressionof tissue near the tip 308 of the fiber 306 according to the method andapparatus of the present invention. As described herein, it will beunderstood that the means for applying mechanical compression of thetissue near the tip 308 of the fiber includes manual compression,mechanical clamps or straps, chemical or other drug-induced swelling,etc.

FIG. 5 is a representative view of the non-contact thermal sensor 600and the cooling system 602 of the method and apparatus of the presentinvention. Non-contact thermal sensors 600 as well as contact devices,including RTDs, are well known in the art. It will be understood thatthe cooling device 602 can be any suitable, controlled device whichallows a predetermined amount of cryogenic fluid to be dispensed from anon-board fluid reservoir or from an external/line source. In a preferredembodiment, the device 602 is computer controlled, to provide spurts orsquirts of cryogenic fluid at a predetermined rate or for apredetermined duration. The cryogenic fluid is dispensed onto thesurface of the skin 604 in an area adjacent the fluid dispensing nozzle606, and the non-contact thermal sensor 600 determines the temperatureof the skin in the same area 604 or in an area 608 distal from the areabeing cooled 604. The present invention, this application and any issuedpatent based hereon incorporates by reference the following issuedpatents with regards surface cooling methods and apparatus utilized inthe present invention: U.S. patent application Ser. No. 08/692,929 filedJul. 30, 1996, now U.S. Pat. No. 5,820,626. U.S. patent application Ser.No. 08/938,923 filed Sep. 26, 1997, now U.S. Pat. No. 5,976,123. U.S.patent application Ser. No. 10/185,490 filed Nov. 3, 1998, now U.S. Pat.No. 6,413,253. U.S. patent application Ser. No. 09/364,275 filed Jul.29, 1999, now U.S. Pat. No. 6,451,007.

FIG. 6 shows curves for absorption coefficients of melanin, hemoglobinand water as a function of wavelength according to the method andapparatus of the present invention. It will be observed in FIG. 6 thatthe region between about 550 nm to about 1060 nm shows high hemoglobinabsorption and low water absorption, as is well known in the prior arttechnology. It will further be observed that the region between about1200 nm to about 1800 nm shows low hemoglobin and higher waterabsorption, which is a key to the present invention.

Clinical Results:

The following is a description of a study undertaken with the financialsupport of the American College of Phlebology BSN-JOBST Phlebology 2006Research Grant.

Our results were presented at the 20th Annual Congress of the AmericanCollege of Phlebology at Sawgrass Marriott Resort and Beach Club, PonteVedra Beach, Fla., Nov. 9-12, 2006.

Objective Summary:

Venous disease was proposed as a cause of Restless Legs Syndrome (RLS)by Dr. Karl A. Ekbom in 1944, but has since remained largely unexplored.This study examines the effect of Endovenous Laser Ablation (ELA) inpatients with concurrent RLS and duplex-proven Superficial VenousInsufficiency (SVI) The aim of this study is to determine what effectELA has in patients with RLS and SVI.

Methods Summary:

Thirty-five patients with moderate to very severe RLS (as defined by the2003 NIH RLS criteria) and duplex-proven SVI completed an InternationalRLS rating scale questionnaire (IRLS) and underwent standard duplexexamination to objectively measure the baseline severity of theirconditions. They were separated into non-operative and operativecohorts. The operative cohort underwent ELA of refluxing superficialaxial veins using the CoolTouch CTEV 1320 nm laser and ultrasound-guidedsclerotherapy of the associated varicose veins with foamed sodiumtetradecyl sulfate (STS). All patients then completed a follow-up IRLSquestionnaire. Baseline and follow-up IRLS scores were compared.

Results Summary:

Operative correction of the SVI decreased the mean IRLS score by 21.4points from 26.9 to 5.5, corresponding to an average 80% improvement insymptoms. Eighty-nine percent of patients enjoyed a decrease in theirscore of ≧15 points. Fifty-three percent of patients had a follow-upscore of ≦5, indicating their symptoms had been largely alleviated, and31% had a follow-up score of zero, indicating complete relief of RLSsymptoms.

Conclusions and Recommendations Summary:

ELA of refluxing axial veins with the CTEV 1320 nm laser and foamed STSsclerotherapy of associated varicosities alleviates RLS symptoms inpatients with SVI and moderate to very severe RLS. Additionally, SVIshould be ruled out in all patients with RLS before initiation orcontinuation of drug therapy.

Patients and Study Design:

We screened 89 patients with complaints of restlessness in their legs.The diagnosis of RLS was determined using the 2003 NIH criteria. Allpatients who met the criteria for RLS were interviewed to confirm thediagnosis of RLS and to exclude conditions that mimic RLS (such aspositional discomfort, neuropathy, night cramps, etc.). They thencompleted an initial IRLS questionnaire to determine the baselineseverity of their disease. Those patients with an IRLS score of 15 orgreater (corresponding with moderate to very severe RLS) underwent ascreening duplex ultrasound. Patients found to have greater than 500milliseconds of reflux in the great saphenous vein (GSV) underwent acomplete duplex evaluation of the deep, superficial, and perforatorsystems. All reflux was mapped for appropriate treatment. Thirty-fivepatients met the criteria and were accepted into the study.

Sixteen patients were assigned to the non-operative cohort, 19 to theoperative cohort. In the non-operative cohort 6.3% of patients were maleand 93.7% were female. The mean age was 58.8, and the average weight180.2 pounds. In the operative cohort, 31.6% of patients were male and68.4% were female. The mean age was 49.4, and the average weight was202.5 pounds. One patient withdrew from each cohort for unrelatedmedical reasons.

Most RLS patients take medication nightly in order to get some sleep. Wefelt it important for this study to be applicable to the broaderpopulation. We therefore did not exclude patients who were taking RLSmedications. In order to stabilize RLS medication as a variable, we didask patients not to add any or discontinue medications known to affectRLS symptoms during the study period.

Intervention:

Patients were assigned to either the non-operative or operative cohort.Non-operative patients completed a follow-up questionnaire six weeksafter the initial questionnaire. This yielded objective measurements ofthe severity of the baseline and final RLS symptoms in the non-operativecohort.

The operative patients underwent ELA of all refluxing axial veins usingthe Cool-Touch 1320 nm laser at settings of 50 Hz and 7 Watts. Thepullback device was set on 0.5 mm/sec for the first 10 cm, then 1.0mm/sec for the remainder of the vein. These laser settings applied 140Joules/cm to the first 10 cm of vein, and 70 Joules/cm to the remainderof the vein (this rather high fluence was utilized to ensure 100%ablation of all treated veins). Varicose veins and refluxing perforatorveins were treated with ultrasound-guided sclerotherapy using 1.0% STSfoam. A 6-inch ACE wrap was applied immediately post-operatively andcontinued for 48 hours, then replaced with 20-30 mm/hg compressionstockings for two weeks. Compression was then removed. Operativepatients underwent a post-operative duplex examination 2-3 days afterthe procedure, and again six weeks later. They completed a final IRLSquestionnaire at the 6-week follow-up appointment. The baseline andfinal IRLS scores of both groups were then compared.

Study Design and Statistical Analysis:

The 35 patients who met the inclusion criteria were enrolled into thisprospective, randomized, unblinded, parallel two-group, pre-post-teststudy. This study design involved outcome variables measured on binomialand continuous scales. For the continuous outcome variables (i.e., IRLSquestionnaire), one-way analysis of variance with two distinct levels ofthe intervention was performed. Moreover, since unequal sample sizeswere anticipated and observations were repeated over time, Bonferroniprocedures were appropriate to control for experimentwise,multi-comparison error. Matched-pairs analysis was used to test the nullhypothesis of zero change from IRLS baseline score.

When analyzing binomial variables (i.e., RLS Symptoms Alleviated, yes orno), Chi-square and likelihood ratio statistics were computed to testthe null hypothesis of no association between the intervention groupsand the response variable(s). In addition, since single-group pre- andpost-test comparisons were performed and the assumption of independentsamples was not met, McNemar's test for matched pairs was appropriate.Exact tests were used and exact probabilities were computed whereappropriate.

All statistical analysis activities were performed using SAS StatisticalSoftware, Version 9.1.3, SAS Institute, Inc., North Carolina, USA. Theprocedures used are PROC ANOVA, PROC GLM, and PROC FREQ.

Results:

Duplex evaluation performed 6 weeks postoperatively revealed that 100%of the treated veins were successfully ablated. Transient postoperativediscomfort in the region of the treated veins was frequently reported.Most patients required only PRN Ibuprofen, foregoing the prescribedhydrocodone. All patients had mild bruising at the access sites. Therewere no major side effects or complications.

When comparing mean baseline IRLS scores for the non-operative andoperative cohorts, 26.8 vs. 26.9 respectively, the difference was notfound to be statistically significant (p=0.971). Consequently, one couldassume homogeneity in RLS symptoms and severity across treatment groupsprior to intervention. At the final evaluation, the mean IRLS score inthe non-operative cohort was actually found to be slightly elevated(28.4) in contrast to their baseline mean score. The mean IRLS score inthe operative cohort decreased by 21.4 points to 5.5. This represents adrop in symptom severity of 80%. The matched-pairs analysis wasstatistically significant (p<0.0001) indicating that the change frombaseline in IRLS score for the operative group was significantly greaterthan the change from baseline in IRLS score for the non-operative group.

Eighty-nine percent of operative patients enjoyed a decrease in theirIRLS score of 15 points or more. Seventy-nine percent of patientsimproved to “mild” disease (final score≦10). Ninety-five percent ofpatients improved to “mild” or “moderate” disease (final score≦20).Fifty-three percent of patients had a final score≦5, indicating theirRLS symptoms had been largely alleviated. Thirty-one percent of patientshad a final score of zero, indicating complete relief of RLS symptoms.

Discussion:

In Dr. K. A. Ekbom's original 1944 article, he presented 8 patients withwhat he called asthenia crurum paraesthetica “irritable legs”. Hedescribed the symptoms RLS and said that, in most patients, objectivesigns were lacking. One (12.5%) of these patients, however, was noted tohave varicose veins. Dr. Ekbom went on to say that all patients hadpalpable dorsalis pedis pulses, yet he concluded “It is possible thatthe condition is due to a functional vascular disorder.” He suspectedvenous congestion and an accumulation of metabolites to be a cause ofRLS. Our study demonstrates that treating the underlying venous diseasecan relieve the RLS symptoms.

Venous insufficiency is an impedance of venous flow back to the heart.It is usually caused by venous reflux secondary to valvular failure andcan occur in the deep, superficial, or perforator veins. Venousinsufficiency results in high venous pressures that are transmitted totributary veins, venules, capillaries and interstitial tissues drainedby the diseased vein. It affects 10-15% of men and 20-25% of women. SVIis much more common than deep venous insufficiency.

According to the Starling concept, most of the fluid forced out of thecapillary bed at the arterial end is normally returned into the lumen atthe venous end. In tissues affected by venous hypertension, thisdelicate balance is disrupted. The high hydrostatic pressure in thevenules and capillaries causes a net increase in the fluid remaining inthe interstitial space. This increased interstitial fluid volumeoverwhelms the lymphatic capacity, resulting in edema formation. As longas the leg is dependant, the interstitial fluid continues to accumulate,until the tissue pressure rises to a point at which the Starlingequilibrium is restored. Considerable edema can accumulate before thispoint of equilibrium is reached. Upon elevation of the leg (such as whenthe patient is lying down or reclining), the venous pressures diminishand the lymphatics can drain the engorged interstitium.

The circadian ebb and flow of edema fluid seen in venous insufficiencyclosely parallels the circadian timing of RLS symptoms. This is morethan mere coincidence. We know that the daily accumulation of softtissue edema creates unpleasant sensations in the legs such asheaviness, fullness, achiness, etc. The nightly receding of that edemafluid somehow causes the “indescribable” sensations that typicallyplague RLS patients. This would explain why the typical RLS symptomsoccur when the patient is reclining and at night, as the elevationmobilizes edema from the legs, and why symptoms seem to wane in theearly morning hours (the edema has largely resolved by that time. Therestless leg movement is a subconscious activation of the musculovenouspump, stretching of afflicted muscles and tendons, or a distractor tomask the tormenting sensations.

This discovery is supported by the fact that 26% of women are affectedby RLS during their pregnancy. Pregnancy has been shown to exacerbateboth RLS and edema independently. Strong correlation is noted with thethird trimester of pregnancy (when the pregnancy-associated edema is atits peak) and tends to disappear with delivery (when thepregnancy-associated edema has receded).

Similar findings are seen in hemodialysis patients. RLS affects 20-80%of this population. Despite extensive research of various clinical andbiochemical parameters, the cause of RLS in this population remainsunknown. It has been shown that increasing dialysis from 3 days a weekto 5 days a week (but not changing total number of hours per week)relieves the RLS symptoms. RLS symptoms disappear in hemodialysispatients who receive a kidney transplant. Frequent dialysis dampens andrenal transplant eliminates the huge volume swings normally seen inhemodialysis patients, thus impacting their RLS symptoms.

Primary RLS is generally felt to be a condition in which an abnormalnervous system is reacting inappropriately to relatively normal legs. InRLS patients with venous disease, it appears that RLS is due to arelatively normal nervous system reacting appropriately to abnormallegs.

Strengths and Limitations of the Study:

We employed the NIH criteria to make the diagnosis of RLS and the IRLSquestionnaire to grade the severity of symptoms. These tools are widelyutilized in current RLS research. They made possible accuratecomparisons between operative and control groups. This allowed us togather statistically significant results despite our small sample size.

Bias was introduced in this study by including only those RLS patientswith duplex-proven SVI. All RLS patients with normal venous functionwere therefore excluded. Bias was also introduced in the manner in whichthe patients were assigned to operative vs. nonoperative cohorts.Medicare and third party insurance carriers require a three to six monthtrial of “conservative non-operative measures”. Because of timeconstraints, patients who had not met these criteria before presentingto our vein center were automatically placed in the non-operativecohort. Patients who had met these mandates were placed in the operativecohort. Further study will explore the connections between RLS, venousinsufficiency, and lower extremity edema.

CONCLUSIONS

Our results demonstrate that ELA of refluxing axial veins andsclerotherapy of associated varicosities alleviates or relieves RLSsymptoms in patients with moderate to very severe RLS and SVI. All RLSpatients should be properly evaluated for venous insufficiency by atechnician familiar with techniques to detect venous reflux beforeinitiation or continuation of drug therapy. Any RLS patient with venousinsufficiency should be referred for evaluation and treatment by aphlebologist. Following these methods and procedures, these patients canescape the nightly torment of chronic RLS.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the present invention belongs. Although any methods andmaterials similar or equivalent to those described can be used in thepractice or testing of the present invention, one methods and materialsare now described. All publications and patent documents referenced inthe present invention are incorporated herein by reference.

While the principles of the invention have been made clear inillustrative embodiments, there will be immediately obvious to thoseskilled in the art many modifications of structure, arrangement,proportions, the elements, materials, and components used in thepractice of the invention, and otherwise, which are particularly adaptedto specific environments and operative requirements without departingfrom those principles. The appended claims are intended to cover andembrace any and all such modifications, with the limits only of the truepurview, spirit and scope of the invention.

1. A method for treatment of restless leg syndrome in a patient withreflux in a leg vein, the method comprising the following steps: A.Performing an exam of veins contributing to vascular insufficiency andreflux; B. Obtaining percutaneous access of the vessel being treatedusing a Seldinger or equivalent technique; C. Advancing a catheter withcatheter tip through an introducer sheath until it is approximately 1-2cm below the saphenofemoral junction (SFJ) or the saphenopoplitealjunction (SPJ) or at the appropriate distance based on the junction orvein being treated; D. Confirming position of the catheter tip such aswith ultrasound, aiming beam visualization, or equivalent; E. Drainingblood from the vein using elevation, suction, compression, vein spasm,or other technique; F. Injecting local anesthesia around the vein beingtreated; and G. Initiating treatment with a device which emits a diodelaser or other laser source, electrical current, radiofrequency waves,microwaves, ultrasound or other source of electromagnetic energy whichpenetrates into regions of tissue.
 2. The method of claim 1 furthercomprising the step of increasing wattage of energy delivered to tissueas desired.
 3. The method of claim 1 further comprising the step ofdetermining endpoint of treatment by observing indications of adequatetissue response, such as slowing or stopping of forward movement offlow, thickening of the vein wall, contracting of the vein, anddecreasing size of the lumen of the vein.
 4. The method of claim 1further comprising the step of determining successful treatment byobserving, such as with ultrasound, following treatment, any one of thegroup consisting of vein appearing more dense and thickened (moreechogenic), vein less compressible with pressure from the ultrasoundprobe, vein lumen is noticeably smaller in size, and vein does notdemonstrate spontaneous flow.